Dry eye is thought to stem from abnormalities of the tear film on the surface of the eye. The tear film includes three layers, an inner mucus layer, an outer lipid layer, and an aqueous layer between them. The mucus layer, which is primarily composed of mucins, is the thinnest layer and functions to adhere the tear film to the eye.
Mucins are high molecular weight glycoproteins that have various functions. Some mucins are secreted into the mucous layer while others form the glycocalyx (transmembrane mucins), which is the specific structure that adheres the tear film to the eye. The glycocalyx is partially embedded in the lipid bilayer of corneal and conjunctival epithelial cells and forms a hydrophilic network that binds secreted mucins in the mucus layer to these cells. Additionally, the mucins in the mucus layer and glycocalyx are believed to attract water, thereby decreasing the surface tension of the tear film and facilitating the even spread of the aqueous layer on the eye, which in turn may protect the eye from pathogens and make the ocular surface less susceptible to damage. Mucins that have been detected in the tear film include MUC1, MUC2, MUC4, MUC5AC, MUC7, MUC13, MUC15, MUC16, and MUC 17. Transmembrane mucins include MUC1, MUC4, MUC13, MUC15, MUC16, and MUC17. Secreted mucins include MUC2, MUC5AC, and MUC7, which can be further classified as gel-forming or soluble. MUC5AC has been identified as a secreted, gel-forming mucin. Mucins found on the ocular surface are primarily produced by goblet cells (e.g., secreted mucin MUC5AC), apical cells of the conjunctiva and cornea (e.g., transmembrane mucins MUC1, MUC2 and MUC4), and the lacrimal gland (e.g., secreted mucin MUC7). In addition to mucins, the lacrimal gland secretes proteins into the aqueous layer that promote spreading of the tear film and that help maintain a healthy environment on the ocular surface. Exemplary proteins include lysozyme, lactoferrin, tear specific prealbumin, caeruloplasmin, lacitin, lipophilin, and immunoglobulins A, D, G, and E.
Decreased mucin and tear protein levels have been associated with dry eye. Common treatment approaches are typically palliative in nature, attempting to supplement the patient's natural tears or improve the residence time of the limited tear volume already present on the ocular surface (Dry Eye Workshop 2007. The Epidemiology of Dry Eye Disease. Ocul. Sur. 2007; 5(2): 93-107). These treatment approaches have had limited success. It would therefore be desirable to have an improved treatment that increases mucin and other tear protein levels in the tear film.